Hypersaline mariculture wastewater necessitates treatment prior to its discharge into marine environments. Algal-mycelial pellets (AMPs), known for their cost-effectiveness, energy efficiency and sustainability, have not been previously explored for their flocculation and pollutant removal capabilities in hyperhaline conditions. This work employed an orthogonal test design to investigate the effects of nine factors at three levels on the treatment efficiency of mariculture wastewater using Chlorella sp. TNBR1 and Aspergillus niger AMPs. The comprehensive optimal conditions for achieving the highest flocculation efficiency and pollutant removal are determined to be a temperature of 30 °C, light intensity of 6000 lux, a 12:0 light-dark cycle, an initial pH of 6, a microalgal density of 11.25 × 10 cell/mL, microalgal growth phase at the early logarithmic stage, a fungal spore density of 9.00 × 10 spore/mL and a fungal pellet phase of 60 h. Under such conditions, the treatment of nonsterile actual mariculture wastewater with Chlorella sp. TNBR1 and Aspergillus niger AMPs results in a 93.35 %±7.20 % reduction in chemical oxygen demand (COD), 92.83 %±7.29 % reduction in total nitrogen (TN), 100 % removal of total phosphorus (TP), and a flocculation efficiency of 69.21 %±5.36 %. These findings confirm that AMPs are a viable solution for effectively treating COD, TN and TP in real hypersaline mariculture wastewater, while also facilitating the flocculation and harvesting of microalgae.